α-Arylation of diethyl malonate via enolate with bases in a heterogeneous phase

Article abstract of DOI:10.1016/S0040-4039(02)00314-3

The influence of various heterogeneous bases on yield and selectivity in the α-arylation of diethyl malonate was studied. Barium hydroxide was found to provide excellent results in this context. The bases used can be easily removed from the reaction medium by filtration.

Full text of DOI:10.1016/S0040-4039(02)00314-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2847–2849
a-Arylation of diethyl malonate via enolate with bases in a
heterogeneous phase
Mar´ıa A. Aramend´ıa, Victoriano Borau, Ce´sar Jime´nez, Jose´ M. Marinas, Jose´ R. Ruiz and
Francisco J. Urbano
Departamento de Qu´ımica Orga´nica, Universidad de Co´rdoba, Campus de Rabanales, Edificio C-3, Ctra. Nnal. IV, km 396,
14014 Co´rdoba, Spain
Received 13 February 2002; accepted 14 February 2002
Abstract—The influence of various heterogeneous bases on yield and selectivity in the a-arylation of diethyl malonate was studied.
Barium hydroxide was found to provide excellent results in this context. The bases used can be easily removed from the reaction
medium by filtration. © 2002 Elsevier Science Ltd. All rights reserved.
Carbon–carbon coupling techniques are of special
interest for the production of fine chemicals. Palladium
is the most flexible and widely used metal for this
purpose. In fact, Pd has been used in Heck,1,2
carbonylation3,4 and arylation reactions.5,6 Specifically,
this metal has received special attention in recent years
as a catalyst for the preparation of a-arylcarbonyl
compounds; also, a large number of arylation reagents
have been reported which, however, are of limited
interest as they must be specific for the particular
a-arylcarbonyl compound.
tural and surface properties,9–12 in the last few years. In
this work, a heterogenous solid of this type was for the
first time used instead of the homogenous bases (metal
alkoxides preferentially) usually employed for this
purpose.
Diethyl malonate was chosen as reactant on the
grounds of its symmetry; this facilitates the analysis of
its reaction products, which possess no regioisomers.
In the literature, the palladium-catalyzed arylation of
carbonyl compounds is described as a carbon–carbon
coupling reaction between an aryl halide and an enolate
(Scheme 2) that takes place in situ in the presence of an
appropriate base.6 As noted earlier, this initial work
focussed on the influence of the base on conversion and
selectivity in the process. To this end, we tested various
solids containing surface basic groups. Table 1 shows
the conversion and selectivity results obtained in the
reaction of bromobenzene with diethyl malonate. As
can be seen, with the exception of three solids (entries
7, 8 and 9 in Table 1), all bases provided rather poor
diethyl phenylmalonate yields as they were unable to
form the enolate of diethyl malonate to an adequate
extent; this resulted in a poor yield in the subsequent
This paper reports the results obtained in the direct
arylation of carbonyl compounds via an enolate species
using a palladium catalyst and a base in a heterogenous
phase. This procedure improves on existing alternatives
as the base can be removed from the medium simply by
filtration once the reaction is finished. We used the
arylation of diethyl malonate with bromobenzene as
model reaction (Scheme 1), sodium tetrachloropalladate
as catalyst and N,N-dimethylacetamide (DMAc) as sol-
vent, as well as various solid bases to obtain the enolate
form. The solids tested had previously been successfully
used in a number of organic processes involving car-
banions.7–10 The authors themselves have employed
some, which they have characterized as regards struc-
Scheme 1. The a-arylation process studied.
Keywords: coupled reactions; Pd catalyst; arylation; diethyl malonate.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00314-3

2848
M. A. Aramend´ıa et al. / Tetrahedron Letters 43 (2002) 2847–2849
Scheme 2. Proposed reaction pathway for the Pd-catalysed a-arylation of carbonyl compounds (as applied to the reaction between
diethyl malonate and bromobenzene).
Table 1. Results obtained in the arylation of diethyl mal-
onate with bromobenzene using Na2PdCl4 as catalyst and
various heterogeneous basesa
Table 2. Results obtained in the arylation of diethyl mal-
onate with arylbenzenes using Na2PdCl4 and Ba(OH)2 as
catalysts
Entry
Base/catalyst
Yield GC (%)b Selectivity (%)c
X-Benzene
Yield (%)
Selectivity (%)
1
2
3
4
5
6
7
8
MgO/Al2O3
MgO/Ga2O3
MgO/CaO
MgO
Ca(OH)2
Ba(OH)2
K2CO3
16.5
8.3
6.5
6.0
96.1
99.0
93.1
41.7
92
87
89
93
94
97
94
91
92
–
Iodobenzene
Bromobenzene
Chlorobenzene
100
99
93
98
97
97
Once Ba(OH)2 was found to be the solid providing the
best results, we used it in the reaction of other arylben-
zenes. Table 2 shows the results obtained; as can be
seen, both yield and selectivity were excellent for the
three arylbenzenes studied.
Na2CO3
Li2CO3
9
10
11
14.3
No reaction
No reaction
Blank-1d
Blank-2e
–
a Reaction conditions: 10 mmol diethyl malonate, 15 mmol bro-
mobenzene, 2% mol Pd, 20 mmol base, 6 mL DMAc.
b Diethyl phenylmalonate yield at 24 h of reaction (20 and 14 h for
entries 5 and 6, respectively).
In summary, the combined use of a heterogeneous base
and a homogeneous catalyst provides extremely good
results in the a-arylation of diethyl malonate. Work
currently in progress is being focussed on the prepara-
tion of products of interest to various chemical indus-
tries (foods, perfumes) using this procedure and on the
heterogenization of the homogeneous catalytic step
with a view to advancing further in the separation of
the reaction products.
c Selectivity towards diethyl phenylmalonate.
d Blank containing no base.
e Blank containing no palladium.
carbon–carbon coupling reaction. This outcome may
have been the result of the solids used only being
effective carbanion-forming agents at higher tempera-
tures. In fact, most reported carbanionic processes
involving these solids take place at temperatures above
300°C and our reactions were conducted at only 100°C.
However, as stated above, both calcium and barium
hydroxide, and potassium carbonate, gave good yield
and selectivity results (particularly barium hydroxide,
which provided conversions near 100% after 14 h of
reaction).
Acknowledgements
The authors gratefully acknowledge funding by Spain’s
Ministerio de Ciencia y Tecnolog´ıa and the Plan
Nacional de Investigacio´n, Desarrollo e Innovacio´n
Tecnolo´gica (Project BQU-2001-2605), as well as by the
Consejer´ıa de Educacio´n y Ciencia de la Junta de
Andaluc´ıa.

M. A. Aramend´ıa et al. / Tetrahedron Letters 43 (2002) 2847–2849
1987, 43, 2335.
2849
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